Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD. | Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD. Park SH, Helsley RN, Fadhul T, Willoughby JLS, Noetzli L, Tu HC, Solheim MH, Fujisaka S, Pan H, Dreyfuss JM, Bons J, Rose J, King CD, Schilling B, Lusis AJ, Pan C, Gupta M, Kulkarni RN, Fitzgerald K, Kern PA, Divanovic S, Kahn CR, Softic S., | 09/6/2023 |
Ketohexokinase-C regulates global protein acetylation to decrease carnitine palmitoyltransferase 1a-mediated fatty acid oxidation. | Ketohexokinase-C regulates global protein acetylation to decrease carnitine palmitoyltransferase 1a-mediated fatty acid oxidation. Helsley RN, Park SH, Vekaria HJ, Sullivan PG, Conroy LR, Sun RC, Romero MDM, Herrero L, Bons J, King CD, Rose J, Meyer JG, Schilling B, Kahn CR, Softic S., Free PMC Article | 08/24/2023 |
Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction. | Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction. Andres-Hernando A, Orlicky DJ, Kuwabara M, Ishimoto T, Nakagawa T, Johnson RJ, Lanaspa MA., Free PMC Article | 11/13/2021 |
studies suggest that it is the inhibition of the Khk C isoform, not the A isoform, that protects animals from Hereditary fructose intolerance. | Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice. Lanaspa MA, Andres-Hernando A, Orlicky DJ, Cicerchi C, Jang C, Li N, Milagres T, Kuwabara M, Wempe MF, Rabinowitz JD, Johnson RJ, Tolan DR., Free PMC Article | 09/14/2019 |
Manual correction of the input Khk gene model provided a much more accurate estimation of relative Khk isoform expression when compared to quantitative PCR. | Correction of gene model annotations improves isoform abundance estimates: the example of ketohexokinase ( Khk). Chabbert CD, Eberhart T, Guccini I, Krek W, Kovacs WJ., Free PMC Article | 09/7/2019 |
These results suggest that KHK-C might play a deleterious role in diabetic kidney disease progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of diabetic kidney disease. | Lacking ketohexokinase-A exacerbates renal injury in streptozotocin-induced diabetic mice. Doke T, Ishimoto T, Hayasaki T, Ikeda S, Hasebe M, Hirayama A, Soga T, Kato N, Kosugi T, Tsuboi N, Lanaspa MA, Johnson RJ, Kadomatsu K, Maruyama S., Free PMC Article | 02/23/2019 |
This studies provided the first evidence that fructokinase modulates vasopressin synthesis in the SON and secretion from the posterior pituitary into circulation. | Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice. Song 宋志林 Z, Roncal-Jimenez CA, Lanaspa-Garcia MA, Oppelt SA, Kuwabara M, Jensen T, Milagres T, Andres-Hernando A, Ishimoto T, Garcia GE, Johnson G, MacLean PS, Sanchez-Lozada LG, Tolan DR, Johnson RJ., Free PMC Article | 09/23/2017 |
Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. | Aging-associated renal disease in mice is fructokinase dependent. Roncal-Jimenez CA, Ishimoto T, Lanaspa MA, Milagres T, Hernando AA, Jensen T, Miyazaki M, Doke T, Hayasaki T, Nakagawa T, Marumaya S, Long DA, Garcia GE, Kuwabara M, Sánchez-Lozada LG, Kang DH, Johnson RJ., Free PMC Article | 07/29/2017 |
Feedforward upregulation of fructolytic and gluconeogenic enzymes specifically requires GLUT5 and KHK and may proactively enhance the intestine's ability to process anticipated increases in dietary fructose concentrations. | Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK. Patel C, Douard V, Yu S, Tharabenjasin P, Gao N, Ferraris RP., Free PMC Article | 04/30/2016 |
Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. | Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK-/- and GLUT5-/- mice. Patel C, Sugimoto K, Douard V, Shah A, Inui H, Yamanouchi T, Ferraris RP., Free PMC Article | 02/13/2016 |
myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1alpha (HIF1alpha) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C | HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease. Mirtschink P, Krishnan J, Grimm F, Sarre A, Hörl M, Kayikci M, Fankhauser N, Christinat Y, Cortijo C, Feehan O, Vukolic A, Sossalla S, Stehr SN, Ule J, Zamboni N, Pedrazzini T, Krek W., Free PMC Article | 08/1/2015 |
Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. | Fructokinase activity mediates dehydration-induced renal injury. Roncal Jimenez CA, Ishimoto T, Lanaspa MA, Rivard CJ, Nakagawa T, Ejaz AA, Cicerchi C, Inaba S, Le M, Miyazaki M, Glaser J, Correa-Rotter R, González MA, Aragón A, Wesseling C, Sánchez-Lozada LG, Johnson RJ., Free PMC Article | 05/16/2015 |
This study demonstrates that blocking KHK and redirecting fructose metabolism to alternative pathways is an effective way to prevent visceral obesity and insulin resistance induced by high fructose, a widespread component of Western diets. | Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway. Marek G, Pannu V, Shanmugham P, Pancione B, Mascia D, Crosson S, Ishimoto T, Sautin YY. | 04/4/2015 |
These studies identify fructokinase as a novel mediator of diabetic nephropathy and document a novel role for endogenous fructose production, or fructoneogenesis, in driving renal disease. | Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy. Lanaspa MA, Ishimoto T, Cicerchi C, Tamura Y, Roncal-Jimenez CA, Chen W, Tanabe K, Andres-Hernando A, Orlicky DJ, Finol E, Inaba S, Li N, Rivard CJ, Kosugi T, Sanchez-Lozada LG, Petrash JM, Sautin YY, Ejaz AA, Kitagawa W, Garcia GE, Bonthron DT, Asipu A, Diggle CP, Rodriguez-Iturbe B, Nakagawa T, Johnson RJ., Free PMC Article | 01/10/2015 |
High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. | High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Ishimoto T, Lanaspa MA, Rivard CJ, Roncal-Jimenez CA, Orlicky DJ, Cicerchi C, McMahan RH, Abdelmalek MF, Rosen HR, Jackman MR, MacLean PS, Diggle CP, Asipu A, Inaba S, Kosugi T, Sato W, Maruyama S, Sánchez-Lozada LG, Sautin YY, Hill JO, Bonthron DT, Johnson RJ., Free PMC Article | 03/15/2014 |
Fructose-induced metabolic syndrome is prevented in mice lacking both fructokinase B and A but is exacerbated in mice lacking fructokinase A. | Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice. Ishimoto T, Lanaspa MA, Le MT, Garcia GE, Diggle CP, Maclean PS, Jackman MR, Asipu A, Roncal-Jimenez CA, Kosugi T, Rivard CJ, Maruyama S, Rodriguez-Iturbe B, Sánchez-Lozada LG, Bonthron DT, Sautin YY, Johnson RJ., Free PMC Article | 05/12/2012 |
These studies are the first demonstration that neither Khk isoform is required for normal growth and development. | Both isoforms of ketohexokinase are dispensable for normal growth and development. Diggle CP, Shires M, McRae C, Crellin D, Fisher J, Carr IM, Markham AF, Hayward BE, Asipu A, Bonthron DT. | 03/5/2011 |